Adeno-associated viral vector gene transfer into leptomeningeal xenografts

Leptomeningeal carcinomatosis is a painful and debilitating complication of cancer. Indwelling reservoirs provide continuous assess to the subarachnoid space, making leptomeningeal cancer potentially amenable to gene therapy. Adeno-associated virus (AAV) is a defective virus not associated with any...

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Bibliographic Details
Published in:Journal of neuro-oncology 1997-09, Vol.34 (2), p.139-144
Main Authors: ROSENFELD, M. R, BERGMAN, I, SCHRAMM, L, GRIFFIN, J. A, KAPLITT, M. G, MENESES, P. I
Format: Article
Language:English
Subjects:
Adenovirus E1A Proteins - biosynthesis
Animals
Antigens, Viral, Tumor - biosynthesis
beta-Galactosidase - analysis
beta-Galactosidase - biosynthesis
Biological and medical sciences
Brain cancer
Cell Line
Cerebellar Neoplasms - pathology
Cerebellar Neoplasms - therapy
Dependovirus
Expression vectors
Gene therapy
Gene Transfer Techniques
Genetic Therapy - methods
Genetic Vectors
Humans
Injections, Intraventricular
Kidney
LacZ gene
Medical sciences
Medulloblastoma
Medulloblastoma - pathology
Medulloblastoma - therapy
Meningeal Neoplasms - pathology
Meningeal Neoplasms - therapy
Meninges
Neurology
Parenchyma
Rats
Recombinant Proteins - analysis
Recombinant Proteins - biosynthesis
Subarachnoid Space
Toxicity
Transplantation, Heterologous
Tumor Cells, Cultured
Tumors
Tumors of the nervous system. Phacomatoses
Xenografts
β-Galactosidase
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Description
Summary:Leptomeningeal carcinomatosis is a painful and debilitating complication of cancer. Indwelling reservoirs provide continuous assess to the subarachnoid space, making leptomeningeal cancer potentially amenable to gene therapy. Adeno-associated virus (AAV) is a defective virus not associated with any human disease. We used an AAV vector to transduce medulloblastoma (DAOY) cells in a nude rat model of leptomeningeal disease. After intraventricular injection of vector carrying the bacterial lacZ gene, beta-galactosidase positive cells were found in the implanted tumor and in ependymal and subependymal cells but not in underlying normal brain parenchyma. No evidence of virally-mediated toxicity was noted in the animals. The results of this pilot study demonstrate that AAV vectors may be used to transfer and express foreign genes in established leptomeningeal tumors.
ISSN:0167-594X
1573-7373
DOI:10.1023/A:1005702228721